Rationale
Despite androgen-deprivation therapy, the adrenal glands and prostate cancer cells continue making small amounts of androgens. Abiraterone inhibits production of testosterone throughout the body by blocking an enzyme that converts other hormones to testosterone. The U.S. Food and Drug Administration previously approved abiraterone for patients with metastatic prostate cancer that worsened despite androgen-deprivation therapy. Addition of abiraterone acetate (Zytiga) plus prednisone to standard hormonal therapy for men newly diagnosed with high-risk, metastatic prostate cancer lowers the chance of death by 38%.

About the study
LATITUDE is a multinational, randomized placebo-controlled phase III clinical trial of men with newly diagnosed, high-risk metastatic prostate cancer who had not previously received androgen-deprivation therapy. All patients had at least two of three risk factors: Gleason score of 8 or more, 3 or more bone metastases, or 3 or more visceral metastases.

The patients were randomly assigned to receive androgen-deprivation therapy plus abiraterone and prednisone or androgen-deprivation therapy plus placebo. Corticosteroid prednisone is routinely given with abiraterone to manage certain side effects of abiraterone, such as low potassium or high blood pressure.

Key Findings

At a median follow-up of 30.4 months, men who received abiraterone had a 38% lower risk of death than those who received placebo.

The median overall survival had not yet been reached in the abiraterone group and was 34.7 months in the placebo group.

Abiraterone was also associated with a 53% lower risk of the cancer worsening and resulted in cancer growth being delayed by a median of 18.2 months.

Several severe side effects were more common with abiraterone acetate and prednisone than placebo: high blood pressure (in 20% vs 10% of men), low potassium level (10.4% vs 1.3%), and liver enzyme abnormalities (5.5% vs 1.3%).

Conclusion
In the phase III clinical trial LATITUDE of 1,200 men with newly diagnosed, high-risk metastatic prostate cancer who had not previously received androgen-deprivation therapy, abiraterone more than doubled the median time until the cancer worsened, from 14.8 months to 33 months.